DNA study redefines meaning of ‘Mexican’

LOS ANGELES TIMES

LOS ANGELES—Writers, artists and historians have long pondered what it means to be Mexican. Now science has offered its answer, and it could change how medicine uses racial and ethnic categories to assess disease risk, testing and treatment.

The broadest analysis of the Mexican genome ever undertaken reveals a nation of staggering genetic diversity, where European conquest only thinly masks the ancestral DNA of Native Americans, and where some populations remain as distinct from one another as Europeans are from Chinese, according to findings published Thursday in the journal Science.

Forty researchers, who share Latino heritage as well as professional qualms over the significance of ethnic and racial categories, teamed up across borders to analyze more than 1 million variations in the building blocks of DNA. They examined more than 500 samples collected in Mexico’s remote Indian villages and polyglot cities, and from Mexican Americans in California.

“Because these populations are so rich, so genetically differentiated, you can’t just lump them all in,” said lead investigator Carlos Bustamante, a population geneticist and co-director of Stanford University’s Center for Computational, Evolutionary and Human Genomics. “You really have to embrace that diversity and think about doing medical genetic studies on a very large scale.”

To illustrate their point, the researchers compared their new genetic data with the results of lung function tests for children in Mexico City and Latinos in the San Francisco Bay Area. They discovered that pulmonary function varied in ways that were mirrored in DNA. It was as if someone with a fraction of Maya ancestry had lungs that were 10 years older than someone with a bit of northern indigenous heritage.

Those results could affect how doctors define “normal” ranges on such tests, and thus diagnoses and treatment for common conditions such as asthma and pulmonary obstruction, said Dr. Esteban Gonzalez Burchard, a University of California, San Francisco asthma researcher and one of the study’s coauthors.

“We’re pushing the ball down the field toward precision medicine,” he said. “We actually just care about what your ancestry is at a particular gene.”

Indeed, it turns out that the genetic meaning of “Mexican” is quite complicated. The variation among indigenous populations, for instance, gets sharper by distance — a gradient that runs roughly parallel to Mexico’s northwest-to-southeast mountain ranges. So a Seri from the Gulf of California area varies as much from a Lacandon Maya near Guatemala as a white person does from an Asian, researchers found.

But Mexico is a land of mixture, captured in the term “mestizo” that describes someone of European and Native-American heritage. The researchers wondered whether the genetic signature of the Aztec, Maya and other cultures had been overwhelmed by the genes of the Spanish conquistadors over the course of the last half millennium.

They were shocked to find that the indigenous component of mestizo samples replicated the same geographic differences found in the indigenous samples. Conquest had not swamped the genetic signal of ancient Mexico.

“To find that substructure being preserved in modern-day populations tells you about the deep roots that these populations have,” said Dr. Andres Moreno-Estrada, a population geneticist in Bustamante’s lab and lead author of the study.

Bustamante and Burchard have long pressed to expand genomic studies, which have been overwhelmingly skewed toward populations of European lineage.

Last year, they revealed a mind-boggling range of gene flow in the Caribbean, where Amazonians apparently mixed with islanders and Mesoamerican mainlanders — even before European conquerors arrived and slave traders brought divergent populations of Africans to the New World.

The resultant genetic diversity all but mocks the medical relevance of the term “Hispanic” to describe millions of people who speak Spanish in 20 countries in the Americas.

“We’re looking beyond race,” Burchard said. “Right now, we still need to use race and ethnicity because they’re proxies, but one day we hope you’ll be able to walk into a clinic and they’ll do genetic testing on you. That’s where we’d like to go.”

Researchers not involved in the study, however, caution that correlations between disease risk and ancestry may not have much of a genetic basis at all. In many cases, they might mask socioeconomic or environmental factors — where and how you live.

The suggestion that differences in DNA are responsible for observed differences in lung capacity “is an enormous leap,” said University of California, Berkeley sociologist Troy Duster, who has written extensively on the intersection of race, biology and public policy.

Lundy Braun, an Africana studies professor at Brown University who studies the intersection of race and medicine, said medicine’s focus on genetics may be overshadowing other avenues of research.

“The effects of social class on lung function have been largely ignored in favor of the focus on race and ethnic difference,” she said.

Braun and Duster worry that such genomic studies may unwittingly lend legitimacy to widely discredited ideas about racial disparities.

“There is always lurking danger that this kind of research, which emphasizes the genetic structure of ethnic and racial groups, fuels the notion that the biology or genetics of those groups explains their condition,” Duster said.

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